The Yale University, W.M. Keck Biotechnology Resource Laboratory's MS & Proteomics Core has developed a state-of-the-art targeted proteomics workflow that utilizes an emerging mass spectrometry based paradigm for validating and quantitating differential protein expression that provides a potentially important diagnostic tool for identification and confirmation of protein biomarkers from clinical samples. Due to rapid acceptance of this technology from Yale investigators, we are requesting funding for an AB SCIEX 6500 QTRAP hybrid triple quadrupole-linear ion trap mass spectrometer, which would be devoted to meeting the very rapidly increasing need for quantifying the levels of multiple preselected proteins. In addition, we are also requesting an automated sample injector and UPLC system, the nanoACQUITY UPLC manufactured by Waters Corporation, that is needed to interface with the MS and that will provide automated sample handing and peptide separation prior to MS analysis, thus enabling continuous 24/7 analysis of very complex samples. When the requested instrumentation is combined with our in-house developed targeted proteomic service, the resulting platform will enable us to greatly expand targeted proteomics services so they can support the 34 NIH-funded projects directed by 27 investigators from 7 Institutions (Yale University, Wake Forest, Dartmouth College, University of Chicago, Universitat de Barcelona, University of Montana, and New York University) that support this application. These investigators propose to use our targeted proteomic service to advance diverse biomedical research on: Anemia, Aseptic meningitis, Amyotrophic lateral sclerosis, Neuronal development and Degenerative (Alzheimer's, Parkinson's , Prion Diseases), Cancer (angiogenesis, papillomaviruses, and Melanoma), Diabetes, Drug Addiction, Cardiovascular disease, Emphysema, HIV, Malaria, Osteoporosis, Leptospirosis, Synaptic Transmission and Cystic Fibrosis. The requested instrumentation would enable existing and new targeted proteome LC-MRM analyses to be made available to the 461 Yale and 574 non-Yale (1,035 total) principal investigators at 305 institutions in 29 countries who used services provided by the Keck Laboratory in 2012. Progress in this research will advance knowledge of how best to understand, prevent, prognose, and treat human diseases. The requested 6500 QTRAP mass spectrometer (MS) would be unique at Yale University, and would be available to other interested investigators due to its placement in a core facility that accepts samples from across the U.S. and (when needed to keep its instrumentation operating at capacity) from around the world. Thus, the 6500 QTRAP MS would significantly contribute to biomedical research at Yale University and beyond.